Switch peptides

Hentschel J, Krause E, Bomer HG (2006) Switch-peptides to trigger the peptide guided assembly of poly(ethylene oxide)-peptide conjugates into tape structures. J Am Chem Soc... 

Kammerer RA, Steinmetz MO. De novo design of a two stranded coiled-coil switch peptide. J Struct Biol 2006 155 146-153. 

Dos Santos S, Chandravarkar A, Mandal B, Mimna R, Murat K, Saucede L, Telia P, Tuchscherer G, Mutter M (2005) Switch-peptides controlling self-Assembly of amyloid P-derived peptides in vitro by consecutive triggering of acyl migrations. J Am Chem Soc 127 11888-11889... 

Dos Santos, S., Chandravarkar, A., Mandal, B., Minina, R., Murat, K., Saucede, L., Telia, P., Tuchscherer, G., and Mutter, M. "Switch-peptides Controlling self-assembly of amyloid beta-derived peptides in vitro by consecutive triggering of acyl migrations". Am. Chem. Soc. 127(34), 11888-11889 (2005). 

Fig. 11.20 The concept of switch-peptides [207,208] in situ induction of conformational changes by enzyme-triggered acyl migration results in the nucleation of a helix (left) or a c/s-amide bond-induced kink conformation (right) for the breaking of/i-sheet templates (e.g. amyloid fibrils).

In addition to their use in the in situ induction of conformational transitions, switch-peptides (O-acyl isopeptides) may serve as alternative solubilizing technique in peptide synthesis [207-214]. The elaboration of these concepts, notably the rational design of dynamic pharmacophores as new type of therapeutically useful compounds, is the subject of our current research. 

Depsipeptide SPPS methodology, a method for SPPS applicable to difficult sequences arising from aggregation phenomena. It relies on the synthesis of Ser or Thr isopeptide intermediates with a final 0-N acyl migration step. The principle is identical to the O-acyl isopeptide method, also termed click peptide or switch peptide method that were developed independently by different groups. It was, for example, successfully employed to synthesize the extremely difficult WWDomain FBP28 [I. Coin et al.,/. Org. Chem. 2006, 71, 6171]. 

A later paper details the de novo design of peptides that switch between a coiled-coil and a helical-hairpin conformation. The parent peptide (coiled-coil switch peptide) CSP-1 is a parallel dimeric coiled coil, but oxidation of cysteine residues in (he peptide causes the switch to a monomer. It remains ar-helical, although the a-helical content is low. Increasing the loop length gives CSP-3, which is a peptide with a higher helical content. CSP-6, an anagram of CSP-3, is more helical stUl and can be switched between the helical-hairpin and coiled-coil conformations. 

Another highly conserved structural feature of X chains is the sequence between residues 104-111 (123), which is very similar or identical in various mammalian species and in chickens. Hood refers to this sequence as a switch peptide since it occurs at the end of the region. 

The synthesis of the switch peptide follows standard SPPS protocols. Incorporation of the defect can be accomplished in two ways. The peptide strands on either side of the defect can be prepared separately (Fig. 6.12). The amino acid used to introduce the defect (serine, tyrosine or cysteine) has to be N-terminal to one peptide strand and remain N-protected with the enzymatically cleavable protection group. The C-terminus can then be... 

Methods for the preparation of enzyme-sensitive switch peptides. TIS, triisopropylsilane. 

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